一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Oncogene >>article
Oncogene

Oncogene

IF: 7.3
Download PDF

Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis

Published:20 October 2021 DOI: 10.1038/s41388-021-02071-2 PMID: 34671086
Shuyu Yu, Weicheng Zang, Yuchong Qiu, Liming Liao, Xiaofeng Zheng

Abstract

Aberrant regulation of ubiquitination often leads to metabolic reprogramming in tumor cells. However, the underlying mechanisms are not fully understood. Here we demonstrate that OTUB2, an OTU deubiquitinase, is upregulated in colorectal cancer (CRC) and exacerbates the progression of CRC through modulating the aerobic glycolysis. Mechanistically, OTUB2 directly interacts with pyruvate kinase M2 (PKM2) and inhibits its ubiquitination by blocking the interaction between PKM2 and its ubiquitin E3 ligase Parkin, thereby enhancing PKM2 activity and promoting glycolysis. In response to glucose starvation stress, the effect of OTUB2 on PKM2 is enhanced, which confers metabolic advantage to CRC cells. Moreover, OTUB2 depletion reduces glucose consumption, lactate production, and cellular ATP production. OTUB2-knockout CRC cells exhibit attenuated proliferation and migration, as well as an elevated level of apoptosis and increased sensitivity to chemotherapy drugs. Furthermore, in vivo assays show that knockout of OTUB2 inhibits tumor growth in mice. Taken together, these findings reveal the critical role of OTUB2 in the regulation of glycolysis and illustrate the molecular mechanism underlying its role as a negative regulator of PKM2 ubiquitination in CRC, establishing a bridge between OTUB2-regulated PKM2 ubiquitination and altered metabolic patterns in CRC and suggesting that OTUB2 is a promising target for CRC treatment.

Similar articles

IF:4.5

Antimicrobial agent chloroxylenol targets β?catenin?mediated Wnt signaling and exerts anticancer activity in colorectal cancer.

International journal of oncology Qi Sun, Boxin Liu,etc Published: 1 November 2023
IF:5.4

Sodium butyrate in both prevention and supportive treatment of colorectal cancer.

ACS Applied Energy Materials Karolina Ka?mierczak-Siedlecka, Luigi Marano,etc Published: 26 October 2022
都江堰市| 巴林右旗| 五台县| 扎囊县| 新民市| 绵竹市| 湟源县| 武鸣县| 肇庆市| 常宁市| 临猗县| 鹰潭市| 涡阳县| 多伦县| 洛南县| 新乡县| 东宁县| 兴安县| 安福县| 水城县| 香格里拉县| 阿克苏市| 夹江县| 万州区| 金山区| 东宁县| 南京市| 依安县| 商河县| 天长市| 邓州市| 渭南市| 车致| 芜湖市| 安仁县| 八宿县| 佛坪县| 桓仁| 泗洪县| 航空| 巫山县|